Humanigen Inc (HGENQ)

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Humanigen Announces Late-Breaking Presentation at the CHEST Annual Meeting Highlighting C-Reactive Protein as a Biomarker for Identifying Patients Most Likely to Benefit from treatment with Lenzilumab

https://ir.humanigen.com/English/news/news-details/2021/Humanigen-Announces-Late-Breaking-Presentation-at-the-CHEST-Annual-Meeting-Highlighting-C-Reactive-Protein-as-a-Biomarker-for-Identifying-Patients-Most-Likely-to-Benefit-from-treatment-with-Lenzilumab/default.aspx

-Baseline C-reactive Protein (CRP) <150 mg/L identified as the strongest predictor of response to lenzilumab in hospitalized COVID-19 patients

-In this population age <85 years, lenzilumab improved likelihood of survival without ventilation by 3-fold and reduced mortality by 2-fold compared to standard treatment that included remdesivir and steroids

BURLINGAME, Calif.--(BUSINESS WIRE)-- Humanigen, Inc. (Nasdaq: HGEN), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, today announced a late-breaking (LB) presentation of results from the Company’s randomized, double-blind, placebo-controlled LIVE-AIR Phase 3 study at the CHEST Annual Meeting 2021, which is being hosted by the American College of Chest Physicians® (CHEST) virtually from October 17th to October 20th. CHEST includes more than 19,000 physicians, nurses, and respiratory therapists among its members, including more 15,500 U.S-based members and 3,500 members from more than 100 other countries.

The presentation will be delivered by Zelalem Temesgen, MD, Professor of Medicine at Mayo Clinic and Principal Investigator of the LIVE-AIR Phase 3 trial, highlighting the potential utility of CRP as a means to optimize outcomes with lenzilumab in hospitalized COVID-19 patients. The LB abstract entitled: “C-Reactive Protein as a Biomarker for Improved Efficacy of Lenzilumab in COVID-19 Patients: Results from the LIVE-AIR Trial” has been published in the journal CHEST®and can be accessed via this link.1

Lenzilumab has not been authorized or approved for use in any indication by any regulatory agency.

“Our analysis of LIVE-AIR data using CRP<150 mg/L as a cut-off suggests that early use of lenzilumab in COVID-19 patients upon hospitalization can significantly reduce progression of these patients to a hyperinflammatory state that independent research has already shown results in higher rates of invasive mechanical ventilation and death,” said Dale Chappell, Chief Scientific Officer of Humanigen.2 “Our LIVE-AIR study data show lenzilumab reduces CRP levels, and improves clinical outcomes, and this analysis suggests utilization of CRP as a biomarker may offer an effective way to optimize lenzilumab treatment in hospitalized COVID-19 patients, if authorized or approved for use. In our LIVE-AIR trial, 78% of the LIVE-AIR study population had a baseline CRP less than 150mg/L, representing a substantial population.”

Exploratory analysis of LIVE-AIR results in patients with CRP<150 mg/L and aged <85 years of age, which represented 74% of patients with an evaluable CRP at baseline, show lenzilumab improved the likelihood of survival without ventilation by more than 3-fold (OR 3.04; 95% CI: 1.68-5.51, nominal p=0.0003) compared with placebo and mortality was improved by more than 2-fold (OR: 2.22; 95%CI: 1.07-4.67, p=0.034). Response to lenzilumab was observed in the first through third quartiles of baseline CRP with the greatest response observed in those patients treated earlier in the inflammatory process (<41 mg/L, HR:8.33; 41-<79 mg/L, HR:1.60; 79-<137 mg/L, HR: 2.12; >137 mg/L, HR: 1.17)

Overall, the LIVE-AIR study achieved its primary endpoint of survival without ventilation measured through day 28 following treatment (HR: 1.54; 95%CI: 1.02-2.32, p=0.0403).

About use of CRP to identify immune phenotypes in hospitalized COVID-19 patients

Numerous studies in COVID-19 have published data showing CRP levels are strongly associated with severity of disease and worsening clinical outcomes such as respiratory failure and death.2,3,4,5 As an example, last year, independent researchers established an operational definition of COVID-19 hyperinflammation (COV-HI) from emerging evidence that there was an association between biomarkers of inflammation such as CRP and severe disease. To test this hypothesis, these UK-based researchers conducted a retrospective longitudinal cohort study of 269 consecutive patients admitted to study hospitals in March 2020. Results of the study support the concept that a subset of COVID-19 that meet the definition of the hyperinflammatory phenotype, 82% of which met the criteria due to elevated CRP (CRP>150 mg/L), suffer from worse outcomes than those who do not. The study also showed 74% of those requiring elevated respiratory care met the definition of COV-HI by the time they needed the additional support. In addition, meeting the definition of COV-HI (CRP > 150 mg/L) was significantly associated with next-day escalation of respiratory support or death supporting the concept that therapeutic intervention prior to CRP > 150 mg/L may be necessary to provide an adequate therapeutic window in order to prevent progression to mechanical ventilation and death.4

While the LIVE-AIR results, reported above, suggest an improved treatment outcome for patients treated with lenzilumab with CRP<150 mg/L, other studies of immunotherapies like tocilizumab show a differential benefit in patients with CRP>150 mg/L. A large observational study in Spain showed tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16–0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19–0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L.6 Another study of tocilizumab reported the primary endpoint (the proportion of patients who required noninvasive ventilation or intubation or who died at day 14) was achieved in the overall patient population as a result of the disproportionate benefit seen in patients with CRP>150 mg/L, as no benefit was reported in patients with baseline CRP<150 mg/L. Likewise, a survival benefit was observed at day 90 in this same study for those treated with tocilizumab who had baseline CRP>150 mg/L, but not for those with baseline CRP <150 mg/L.7 This suggests CRP as a biomarker may help physicians to determine which immunotherapeutic may be most beneficial for a particular patient.